The goal of this Mentored Patient-Oriented Research Career Development Award (K23) is to allow me to become an independent, transdisciplinary researcher examining sex differences in stress responses and depression over puberty. I am a new Assistant Professor at the Brown University Center for Behavioral and Preventive Medicine with previous research focusing on sex differences in stress responses and depression in adults. Training from this K23 proposal will allow me to re-focus on adolescents and to develop a program of research examining: a) How do HPA responses to stress change across puberty in boys and girls? and b) Do changes in HPA responses to stress over puberty influence the emergence of sex differences in depression? My Career Development Plan includes training in social and biological influences on adolescent development, nosology and measurement of adolescent depression, statistical methods and ethics. My research goals include carrying out the K23 study, building a base of publications in adolescent stress responses and depression, and the submission of an R01. Guiding my training and research will be four transdisciplinary Mentors: Raymond Niaura, Ph.D. (sex differences in stress responses); Ronald Seifer, Ph.D. (high-risk children, statistics, ethics); Ronald Dahl, M.D. (puberty, depression, brain stress systems) and Adrian Angold, MRCPsych (sex differences in depression, nosology, statistics). The Research Plan involves a cross-sectional investigation of sex differences in stress responses across stages of puberty in adolescents at risk for depression (offspring of depressed mothers). I hypothesize that in the early stages of puberty there will be no sex differences in HPA responses to interpersonal and instrumental stress. In advanced puberty, however, paralleling the emergence of sex differences in depression, girls will show greater responses to interpersonal compared to achievement stress, but boys will show greater responses to achievement compared to interpersonal stress. The K23 study will represent pilot data for a longitudinal study of stress responses and depression over puberty (R01 submission). This work has implications for targeted intervention and prevention efforts to diminish sex differences in adolescent depression. It should also elucidate basic interactions between the gonadal and stress axes over puberty.